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. 2025;25(6):746-759.
doi: 10.2174/0115665240304363240524103203.

Iron Overload-induced Ferroptosis as a Target for Protection against Obliterative Bronchiolitis after Orthotopic Tracheal Transplantation in Mice

Yun You  1 , Guoliang Wang  2 , Qi Cui  3 , Xiangfu Sun  4 , Li Wan  4 , Quanchao Sun  4
Affiliations

Iron Overload-induced Ferroptosis as a Target for Protection against Obliterative Bronchiolitis after Orthotopic Tracheal Transplantation in Mice

Yun You et al. Curr Mol Med. 2025.

Abstract

Introduction: The major complication of Obliterative Bronchiolitis (OB) is characterized by epithelial cell loss, fibrosis, and luminal occlusion of the terminal small airways, which limits the long-term survival of the recipient after lung transplantation. However, the underlying mechanisms are still not fully clarified. This research aims to investigate whether iron overload-induced ferroptosis is involved in OB development and provide a new target for OB prevention.

Materials and methods: Allograft orthotopic tracheal transplantation in mice was applied in our study. Ferrostatin-1 and deferoxamine were administrated to inhibit ferroptosis and get rid of ferric iron, while iron dextran was used to induce an iron overload condition in the recipient. The histological examination, luminal occlusion rate, collagen deposition, iron level, ferroptosis marker (GPX4, PTGS2), and mitochondrial morphological changes of the graft were evaluated in mice.

Results: Our research indicated that ferroptosis and iron overload contribute to OB development, while ferroptosis inhibition and iron chelator could reverse the changes. Iron overload exacerbated OB development after orthotopic tracheal transplantation via promoting ferroptosis.

Conclusion: Overall, this research demonstrated that iron overload-induced ferroptosis is involved in OB, which may be a potential therapeutic target for OB after lung transplantation.

Keywords: CLAD; Iron overload; ferroptosis; lung transplantation; obliterative bronchiolitis; tracheal transplantation..

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References

    1. Chambers D.C.; Perch M.; Zuckermann A.; The international thoracic organ transplant registry of the international society for heart and lung transplantation: Thirty-eighth adult lung transplantation report — 2021; Focus on recipient characteristics. J Heart Lung Transplant 2021,40(10),1060-1072 - DOI - PubMed
    1. Avtaar Singh S.S.; Das De S.; Al-Adhami A.; Singh R.; Hopkins P.M.A.; Curry P.A.; Primary graft dysfunction following lung transplantation: From pathogenesis to future frontiers. World J Transplant 2023,13(3),58-85 - DOI - PubMed
    1. Barker A.F.; Bergeron A.; Rom W.N.; Hertz M.I.; Obliterative Bronchiolitis. N Engl J Med 2014,370(19),1820-1828 - DOI - PubMed
    1. Kulkarni H.S.; Cherikh W.S.; Chambers D.C.; Bronchiolitis obliterans syndrome–free survival after lung transplantation: An international society for heart and lung transplantation thoracic transplant registry analysis. J Heart Lung Transplant 2019,38(1),5-16 - DOI - PubMed
    1. Bos S.; Milross L.; Filby A.J.; Vos R.; Fisher A.J.; Immune processes in the pathogenesis of chronic lung allograft dysfunction: Identifying the missing pieces of the puzzle. Eur Respir Rev 2022,31(165),220060 - DOI - PubMed

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